title: Safety biomarkers in preclinical development: translational potential.
abstract: The identification, application, and qualification of safety biomarkers are becoming increasingly critical to successful drug discovery and development as companies are striving to develop drugs for difficult targets and for novel disease indications in a risk-adverse environment. Translational safety biomarkers that are minimally invasive and monitor drug-induced toxicity during human clinical trials are urgently needed to assess whether toxicities observed in preclinical toxicology studies are relevant to humans at therapeutic doses. The interpretation of data during the biomarker qualification phase should include careful consideration of the analytic method used, the biology, pharmacokinetic and pharmacodynamic properties of the biomarker, and the pathophysiology of the process studied. The purpose of this review is to summarize commonly employed technologies in the development of fluid- and tissue-based safety biomarkers in drug discovery and development and to highlight areas of ongoing novel assay development.
authors.affiliation: Discovery and Investigative Safety, Preclinical Safety, Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA. Email: vito.sasseville@novartis.com.
authors.forename: V G
authors.initials: VG
authors.lastname: Sasseville
authors.forename: K G
authors.initials: KG
authors.lastname: Mansfield
authors.forename: D J
authors.initials: DJ
authors.lastname: Brees
mesh_terms: D000818:Animals; D054316:Biomarkers, Pharmacological / Q000032:analysis*; D002986:Clinical Trials as Topic; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D010338:Pathology, Clinical; D057170:Translational Research, Biomedical
chemical_list: D054316:Biomarkers, Pharmacological
keywords: biomarker; clinical pathology; qualification; validation